Stability of 2,5mg folic acid capsules

Camille Fanjeaux, Raphaël Vazquez, Marie-Noëlle Guerrault-Moro, Anne-Claire Lagrave CHI Poissy-Saint-Germain-en-Laye

In neonatal reanimation and neonatology, folic acid (FA) is used to correct macrocytosis anaemias during premature infants first weeks of life when iron injections are not effective to cure them. Then, the usual posology is 2,5 mg/d.
As marketed tablets are dispensed in 5 mg forms, the aim is to elaborate an hospital preparation of 2,5 mg folic acid capsules, to define its assay method and to study its stability over a year.

Capsules of 2,5 mg folic acid were formulated (qs monohydrate lactose to produce 100 capsules n°4). They were packed in opaque blister.
Stability indicative method was developed. Analysis was performed by HPLC-DAD (C18 column, mobile phase water/methanol R 88/12, phosphate buffer). Degradation products were generated by acid (HCl) and basic (NaOH) hydrolysis, photodegradation and oxidation (H2O2). Method was approved : linearity (concentration range [35 - 65] μg/L), matrix effect, reproducibility, repeatability, accuracy.
Stability is studied for 1 year, in 21 ± 2°C and 50 ± 5 % residual humidity. Batch content uniformity was controlled on 10 capsules (PE 2.9.6) then 3 capsules were dosed each day of analysis (D1, D7, D30, D60, D90, D180, D270 et D365).

FA forced degradation about 20% of initial concentration (HCl 0,5 M, H2O2 3 % à 80° C, 15 min exposition to natural light) showed method is indicative of stability with degradation products on chromatograms.
Method is linear in concentration range [35 - 65] μg/L (pvalue > 0,05 alpha risk 5 %), repeatable (CV = 1,84 %), reproducible (CV = 2,12 %) and accurate [98,85 - 101,23] % for target concentration of 50 μg/L. No significant matrix effect was found with a 5 % alpha risk.
During all the study, no degradation product was viewed, and peak’s purity were always verified in each chromatogram.
Content in FA compared to D0 content for 6 months is included within the range of [90 – 110] %.

Folic acid capsules remain stable for, at least, 6 months in an appropriate form for routine use and to anticipate needs of both units.

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